Min-Liang Pan

University of California, Irvine, Irvine, CA, United States

Are you Min-Liang Pan?

Claim your profile

Publications (20)24.96 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: A noninvasive method of monitoring the loss of islet cells can provide an earlier and improved diagnosis for therapeutics development of preclinical phases of diabetes. The use of [18F]fallypride, a dopamine D2/D3 receptor radiotracer, has been developed as a surrogate marker to evaluate loss of pancreatic islet cells in a rodent model of type 1 diabetes. Materials and Methods: Healthy Sprague–Dawley rats were administered [18F]fallypride and imaged for 2 h in a positron emission tomography (PET)/computed tomography (CT) scan. Diabetes was then induced in the same rats by administration of streptozotocin, and a PET/CT scan was performed 4 days after establishing diabetes. Pancreata of a separate set of rats were evaluated by insulin immunostaining for loss of islet cells by streptozotocin. Results: Blood glucose levels of 125 mg/dL and 550 mg/dL were established for those rats without and with diabetes, respectively. [18F]Fallypride uptake in the pancreas of both groups of rats was rapid, but the rats with diabetes showed a significantly lower uptake (less than 50%). The specific binding ratio was decreased by 77% in the diabetic rats. Conclusions: [18F]Fallypride can be a useful surrogate marker for monitoring changes in pancreatic islet cells, thus providing a noninvasive method to evaluate efficacy of therapeutics.
    Diabetes Technology &amp Therapeutics 09/2014; Vol 16(9):in press. · 2.21 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives Spinal cord is known to be innervated with dopaminergic cells with catecholaminergic projections arising from the medulla and pons and dopaminergic transmission in the spinal cord is vital for sensory and motor function. Our goal was to evaluate and compare the imaging capability of dopamine D2/D3 receptors in the rat spinal cord using PET ligands 18 F-fallypride and 11C-fallypride. Methods Male Sprague–Dawley rats were used in all in vitro and in vivo studies. Spinal cord and brain sections were used for in vitro autoradiography and ex vivo autoradiography. For in vivo studies animals received a 18 F-fallypride scan or a 11C-fallypride PET scan. The spinal cord and the brain were then harvested, flash-frozen and imaged ex vivo. For in vivo analysis Logan plots with cerebellum as a reference was used to evaluate binding potentials (BP). Tissue ratios were used for ex vivo analysis. Drug effects were evaluated using clozapine, haloperidol and dopamine were evaluated on spinal cord sections in vitro. Results In vitro studies showed 18 F-fallypride binding to superficial dorsal horn (SDH), dorsal horn (DH), ventral horn (VH) and the pars centralis (PC). In the cervical section, the greatest amount of binding appeared to be in the SDH. Ex vivo studies showed approximately 6% of 18 F-fallypride in SDH compared to that observed in the striatum. In vivo analysis of both 18 F-fallypride and 11C-fallypride in the spinal cord were comparable to that in the extrastriatal regions. Haloperidol and clozapine displaced more than 75% of the 18 F-fallypride in spinal cord sections. Conclusions Our studies showed 18 F-fallypride and 11C-fallypride binding in the spinal cord in vitro and in vivo. The binding pattern correlates well with the known distribution of dopamine D2/D3 receptors in the spinal cord. Keywords Spinal cord; Dopamine receptors; PET; 18 F-fallypride; 11C-fallypride
    Nuclear Medicine and Biology 08/2014; 41(Nov-Dec):841-847. · 2.52 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract: Elevated levels of histone deacetylases (HDACs) have been indicated in the development of some cancers. HDAC has been imaged using 18F-FAHA and may serve as a marker to study epigenetics. We report evaluation of 18F-FAHA as a probe in the early diagnosis of lung cancer using 18F-FAHA PET/CT studies of A/J mice treated with NNK. 18F-FAHA radiosynthesis was carried out in specific activity of ~2 Ci/μmol. A/J mice were divided into 2 groups: 1. Controls; 2. NNK treatment group with NNK (100 mg/kg, ip, weekly for 4 wks). Mice were injected 100-200 μCi i.v. 18F-FAHA and then scanned in Inveon PET/CT under anesthesia using 2.0% isoflurane. Midbrain, cerebellum and brainstem uptake of 18F-FAHA was displaced by the known HDAC inhibitor, suberanilohydroxamic acid (SAHA) with less than 10% activity remaining. CT revealed presence of lung nodules in 8 to 10-month old NNK mice while control mice were free of tumors. Little uptake of 18F-FAHA was observed in the control mice lungs while significant 18F-FAHA uptake occurred in the lungs of NNK-treated mice with tumor/nontumor >2.0. Ex vivo scans of the excised NNK and control mice lungs confirmed presence of extensive amounts of lung nodules seen by CT and confirmed by 18F-FAHA in the NNK mice with tumor/nontumor >6.0. Our preliminary imaging studies with A/J mice lung cancer model suggest 18F-FAHA PET may allow the study of epigenetic mechanisms involved in NNK-induced tumorigenesis in the lungs.
    American Journal of Nuclear Medicine and Molecular Imaging 06/2014; 4(4):324-332.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Background: A noninvasive method of monitoring the loss of islet cells can provide an earlier and improved diagnosis for therapeutics development of preclinical phases of diabetes. The use of [(18)F]fallypride, a dopamine D2/D3 receptor radiotracer, has been developed as a surrogate marker to evaluate loss of pancreatic islet cells in a rodent model of type 1 diabetes. Materials and Methods: Healthy Sprague-Dawley rats were administered [(18)F]fallypride and imaged for 2 h in a positron emission tomography (PET)/computed tomography (CT) scan. Diabetes was then induced in the same rats by administration of streptozotocin, and a PET/CT scan was performed 4 days after establishing diabetes. Pancreata of a separate set of rats were evaluated by insulin immunostaining for loss of islet cells by streptozotocin. Results: Blood glucose levels of 125 mg/dL and 550 mg/dL were established for those rats without and with diabetes, respectively. [(18)F]Fallypride uptake in the pancreas of both groups of rats was rapid, but the rats with diabetes showed a significantly lower uptake (less than 50%). The specific binding ratio was decreased by 77% in the diabetic rats. Conclusions: [(18)F]Fallypride can be a useful surrogate marker for monitoring changes in pancreatic islet cells, thus providing a noninvasive method to evaluate efficacy of therapeutics.
    Diabetes Technology &amp Therapeutics 05/2014; 16(10):640-643. · 2.21 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Brown adipose tissue [BAT] metabolism in vivo is vital for the development of novel strategies in combating obesity and diabetes. Currently, BAT is activated at low temperatures and measured using 2-deoxy-2-18F-fluoro-D-glucose [18F-FDG] positron-emission tomography [PET]. We report the use of b3-adrenergic receptormediated activation of BAT at ambient temperatures using (R, R)-5-[2-[2,3-(3-chlorphenyl)-2-hydroxyethyl-amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate, disodium salt [CL316,243] (a selective b3-adrenoceptor agonist) and measured by 18F-FDG PET/computed tomography [CT]. Methods: Control and CL316,243-treated (2 mg/kg) male Sprague-Dawley rats were administered with 18F-FDG for PET/CT studies and were compared to animals at cold temperatures. Receptor-blocking experiments were carried out using propranolol (5 mg/kg). Dose effects of CL316,243 were studied by injecting 0.1 to 1 mg/kg 30 min prior to 18F-FDG administration. Imaging results were confirmed by autoradiography, and histology was done to confirm BAT activation. Results: CL316,243-activated interscapular BAT [IBAT], cervical, periaortic, and intercostal BATs were clearly visualized by PET. 18F-FDG uptake of IBAT was increased 12-fold by CL316,243 vs. 1.1-fold by cold exposure when compared to controls. 18F-FDG uptake of the CL-activated IBAT was reduced by 96.0% using intraperitoneal administration of propranolol. Average 18F-FDG uptake of IBAT increased 3.6-, 3.5-, and 7.6-fold by doses of 0.1, 0.5,and 1 mg/kg CL, respectively. Ex vivo 18F-FDG autoradiography and histology of transverse sections of IBAT confirmed intense uptake in the CL-activated group and activated IBAT visualized by PET. Conclusion: Our study indicated that BAT metabolic activity could be evaluated by 18F-FDG PET using CL316,243 at ambient temperature in the rodent model. This provides a feasible and reliable method to study BAT metabolism. Keywords: BAT, CL316,243, β3-adrenoceptor, 18F-FDG, obesity
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Brown adipose tissue [BAT] metabolism in vivo is vital for the development of novel strategies in combating obesity and diabetes. Currently, BAT is activated at low temperatures and measured using 2-deoxy-2-18F-fluoro-D-glucose [18F-FDG] positron-emission tomography [PET]. We report the use of b3-adrenergic receptormediated activation of BAT at ambient temperatures using (R, R)-5-[2-[2,3-(3-chlorphenyl)-2-hydroxyethyl-amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate, disodium salt [CL316,243] (a selective b3-adrenoceptor agonist) and measured by 18F-FDG PET/computed tomography [CT]. Methods: Control and CL316,243-treated (2 mg/kg) male Sprague-Dawley rats were administered with 18F-FDG for PET/CT studies and were compared to animals at cold temperatures. Receptor-blocking experiments were carried out using propranolol (5 mg/kg). Dose effects of CL316,243 were studied by injecting 0.1 to 1 mg/kg 30 min prior to 18F-FDG administration. Imaging results were confirmed by autoradiography, and histology was done to confirm BAT activation. Results: CL316,243-activated interscapular BAT [IBAT], cervical, periaortic, and intercostal BATs were clearly visualized by PET. 18F-FDG uptake of IBAT was increased 12-fold by CL316,243 vs. 1.1-fold by cold exposure when compared to controls. 18F-FDG uptake of the CL-activated IBAT was reduced by 96.0% using intraperitoneal administration of propranolol. Average 18F-FDG uptake of IBAT increased 3.6-, 3.5-, and 7.6-fold by doses of 0.1, 0.5,and 1 mg/kg CL, respectively. Ex vivo 18F-FDG autoradiography and histology of transverse sections of IBAT confirmed intense uptake in the CL-activated group and activated IBAT visualized by PET. Conclusion: Our study indicated that BAT metabolic activity could be evaluated by 18F-FDG PET using CL316,243 at ambient temperature in the rodent model. This provides a feasible and reliable method to study BAT metabolism. Keywords: BAT, CL316,243, β3-adrenoceptor, 18F-FDG, obesity
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pharmacologic approaches to study brown adipocyte activation in vivo with a potential of being translational to humans are desired. The aim of this study was to examine pre- and postsynaptic targeting of adrenergic system for enhancing brown adipose tissue (BAT) metabolism quantifiable by [(18)F]fluoro-2-deoxyglucose ([(18)F]FDG) positron emission tomography (PET)/computed tomography (CT) in mice. A β3-adrenoreceptor selective agonist (CL 316243), an adenylyl cyclase enzyme activator (forskolin) and a potent blocker of presynaptic norepinephrine transporter (atomoxetine), were injected through the tail vein of Swiss Webster mice 30minutes before intravenous (iv) administration of [(18)F]FDG. The mice were placed on the PET/CT bed for 30min PET acquisition followed by 10min CT acquisition for attenuation correction and anatomical delineation of PET images. Activated interscapular (IBAT), cervical, periaortic and intercostal BAT were observed in 3-dimentional analysis of [(18)F]FDG PET images. CL 316243 increased the total [(18)F]FDG standard uptake value (SUV) of IBAT 5-fold greater compared to that in placebo-treated mice. It also increased the [(18)F]FDG SUV of white adipose tissue (2.4-fold), and muscle (2.7-fold), as compared to the control. There was no significant difference in heart, brain, spleen and liver uptakes between groups. Forskolin increased [(18)F]FDG SUV of IBAT 1.9-fold greater than that in placebo-treated mice. It also increased the [(18)F]FDG SUV of white adipose tissue (2.2-fold) and heart (5.4-fold) compared to control. There was no significant difference in muscle, brain, spleen, and liver uptakes between groups. Atomoxetine increased [(18)F]FDG SUV of IBAT 1.7-fold greater than that in placebo-treated mice. There were no significant differences in all other organs compared to placebo-treated mice except liver (1.6 fold increase). A positive correlation between SUV levels of IBAT and CT Hounsfield unit (HU) (R(2)=0.55, p<0.001) and between CT HU levels of IBAT and liver (R(2)=0.69, p<0.006) was observed. The three pharmacologic approaches reported here enhanced BAT metabolism by targeting different sites in adrenergic system as measured by [(18)F]FDG PET/CT.
    Nuclear Medicine and Biology 01/2014; 41(1):10-16. · 2.52 Impact Factor
  • Jogeshwar Mukherjee, Min-Liang Pan
    [Show abstract] [Hide abstract]
    ABSTRACT: Various compounds, compositions, and methods for binding to β-amyloid plaque and norepinephrine transporters are presented. Especially preferred compounds include those with a PET-detectable label.
    Ref. No: US 20130315826 A1, Year: 11/2013
  • 60th Annual Meeting of Society of Nuclear Medicine, Vancouver, Canada, June 8-12, 2013, Journal of Nuclear Medicine; 06/2013
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: Alzheimer’s disease (AD) pathology show formation of Aβ-amyloid plaques (Aβ) and neurofibrillary tangles (NFT) which have deleterious effects on neurotransmitter-receptor functions. Our studies report on the interaction between norepinephrine (NE) and Aβ, using radiotracers 11C-PIB, 3H-PIB and 11C-TAZA (4-11C-methyl-4’-N,N-dimethylazodianiline). Methods: Human post-mortem brain sections (AD, n=4, age 77-89, SP Stage C and controls, n=4; age 81-90 SP Stage 0-A) were obtained from UCI ADRC. Hippocampus (HP) and frontal cortex (FC) brain slices (7 μm thick) were washed in TBS and stained with anti-Aβ antibody 4G8. Adjacent slices were incubated with 11C-PIB (5-25 μCi/cc) or 11C-TAZA (25-30 μCi/cc) in 40% ethanol and 3H- PIB (0.03 μCi/cc) in 10% ethanol and 90% PBS at 37 oC for 0.5-1 hr. Competition with NE (10nM- 500μM) was carried out. 10-100 μM PIB was used for nonspecific binding. Regions of interest were drawn and digital light units (DLU)/ mm2 (Optiquant program) were used to quantify the percentage change in binding of the radiotracers. Results: The 4G8 immunostains confirmed the presence of Aβ-amyloid plaques on AD HP and FC sections, while control sections showed minimal plaques. 11C-PIB and 3H-PIB, both showed a consistent >5 ratio between AD versus control brain. The decrease in 11C-PIB binding with the addition of 100μM NE was >50% while the decrease in 3H- PIB binding was >25% in the PBS buffer. Displacement of 11C-PIB and 3H- PIB by NE was dose-dependent, suggesting competitive binding. 11C-TAZA was found to have a decrease in binding of >30%. Because PIB successfully displaced 11C-PIB, 3H- PIB, and 11C-TAZA, it suggests that both tracers may have similar binding sites and thus similar decreasing effect with the addition of NE. Conclusions: Aβ may be a competing binding site for NE and may possibly interrupt NE transmission or have a role in the pathogenesis of AD. 11C/3H-PIB and 11C-TAZA were displaced by NE both in the HP and FC. Further experiments using 3H-NE are underway to examine NE and Aβ interaction. Research Support: NIH/NIA R01AG029479 (JM), R33 AG030524 (JM)
    60th Annual Meeting of Society of Nuclear Medicine, Vancouver, Canada, June 8-12, 2013, Journal of Nuclear Medicine; 06/2013
  • 60th Annual Meeting of Society of Nuclear Medicine, Vancouver, Canada, June 8-12, 2013, Journal of Nuclear Medicine; 06/2013
  • 60th Annual Meeting of Society of Nuclear Medicine, Vancouver, Canada, June 8-12, 2013, Journal of Nuclear Medicine; 06/2013
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Brown adipose tissue (BAT) plays a significant role in metabolism. Here, we report the use of atomoxetine (a clinically applicable norepinephrine reuptake inhibitor) for (18) F-FDG PET imaging of BAT and its effects on heat production and blood glucose concentration. Fasted male Sprague-Dawley rats were administered with intravenous (18) F-FDG. The same rats were treated with atomoxetine (0.1 mg/kg, iv) 30 minutes before (18) F-FDG administration. To confirm the β-adrenergic effects, propranolol (β-adrenergic inhibitor) 5mg/kg was given intraperitoneally 30 minutes prior to atomoxetine administration. The effect of atomoxetine on BAT metabolism was assessed in fasted and non-fasted rats and on BAT temperature and blood glucose in fasted rats. In (18) F-FDG PET/CT images, interscapular BAT (IBAT) and other areas of BAT were clearly visualized. When rats were fasted, atomoxetine (0.1 mg/kg) increased the (18) F-FDG uptake of IBAT by factor of 24 within 30 minutes. Propranolol reduced the average (18) F-FDG uptake of IBAT significantly. Autoradiography of IBAT and white adipose tissue confirmed the data obtained by PET. When rats were not fasted, atomoxetine-induced increase of (18) F-FDG uptake in IBAT was delayed and occurred in 120 minutes. For comparison, direct stimulation of β(3) -adrenreceptors in non-fasted rats with CL316,243 occurred within 30 minutes. Atomoxetine-induced IBAT activation was associated with higher IBAT temperature and lower blood glucose. This was mediated by inhibition of norepinephrine reuptake transporters in IBAT leading to increased norepinephrine concentration in the synapse. Increased synaptic norepinephrine activates β(3) -adrenreceptors resulting in BAT hypermetabolism that is visible and quantifiable by (18) F-FDG PET/CT.
    Synapse 10/2012; · 2.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Nicotinic acetylcholine receptors (nAChRs) are downregulated in disease conditions such as Alzheimer's and substance abuse. Presently, (123)I-5-IA-85380 is used in human studies and requires over 6h of scanning time, thus increases patient discomfort. We have designed and synthesized 3-iodo-5-[2-(S)-3-pyrrolinylmethoxy]pyridine (niodene) with the aim to have faster binding kinetics compared to (123)I-5-IA-85380, which may reduce scanning time and help in imaging studies. Binding affinity K(i) of niodene for rat brain α4β2 receptors in brain homogenate assays using (3)H-cytisine was 0.27nM. Niodene, 10nM displaced >95% of (18)F-nifene bound to α4β2 receptors in rat brain slices. By using the iododestannylation method, (123)I-niodene was obtained in high radiochemical purity (>95%) but with low radiochemical yield (<5%) and low specific activity (∼100Ci/mmol). Autoradiograms show (123)I-niodene localized in the thalamus and cortex, which was displaced by nicotine (thalamus to cerebellum ratio=4; cortex to cerebellum ratio=1.6). Methods of radioiodination need to be further evaluated in order to obtain (123)I-niodene in higher radiochemical yields and higher specific activity of this potentially useful new SPECT imaging agent.
    Bioorganic & medicinal chemistry letters 10/2012; · 2.65 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE: [(18)F]Mefway is a novel radiotracer specific to the serotonin 5-HT(1A) receptor class. In preparation for using this tracer in humans, we have performed whole-body PET studies in mice to evaluate the biodistribution and dosimetry of [(18)F]Mefway. METHODS: Six mice (three females and three males) received IV injections of [(18)F]Mefway and were scanned for 2 h in an Inveon-dedicated PET scanner. Each animal also received a high-resolution CT scan using an Inveon CT. The CT images were used to draw volume of interest on the following organs: the brain, large intestine, stomach, heart, kidneys, liver, lungs, pancreas, bone, spleen, testes, thymus, gallbladder, uterus, and urinary bladder. All organ time-activity curves without decay correction were normalized to the injected activity. The area under the normalized curves was then used to compute the residence times in each organ. Data were analyzed using PMOD and Matlab software. The absorbed doses in mouse organs were computed using the RAdiation Dose Assessment Resource animal models for dose assessment. The residence times in mouse organs were converted to human values using scale factors based on differences between organ and body weights. OLINDA/EXM 1.1 software was used to compute the absorbed human doses in multiple organs for both female and male phantoms. RESULTS: The highest mouse residence times were found in the liver, urinary bladder, and kidneys. The largest doses in mice were found in the urinary bladder (critical organ), kidney, and liver for both females and males, indicating primary elimination via urinary system. The projected human effective doses were 1.21E - 02 mSv/MBq for the adult female model and 1.13E - 02 mSv/MBq for the adult male model. The estimated human biodistribution of [(18)F]Mefway was similar to that of [(11)C]WAY 100,635, a 5-HT(1A) tracer for which dosimetry has been evaluated in humans. CONCLUSIONS: The elimination of radiotracer was primarily via the kidney and urinary bladder with the urinary bladder being the critical organ. Whole-body mouse imaging can be used as a preclinical tool to provide initial estimates of the absorbed doses of [(18)F]Mefway in humans.
    Molecular imaging and biology: MIB: the official publication of the Academy of Molecular Imaging 07/2012; · 2.47 Impact Factor
  • 59th Annual Meeting of Society of Nuclear Medicine, Miami, Florida, June 9-13, 2012, Journal Nuclear Medicine; 06/2012
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Islet cell loss in the pancreas results in diabetes. A noninvasive method that measures islet cell loss and also tracks the fate of transplanted islets would facilitate the development of novel therapeutics and improve the management of diabetes. We describe a novel dopamine D(2)/D(3) receptor (D(2)/D(3)R)-based PET method to study islet cells in the rat pancreas and in islet cell transplantation. (18)F-fallypride binding to isolated rat islets and pancreas was evaluated in the absence and presence of the D(2)/D(3)R inhibitor haloperidol. After intravenous (18)F-fallypride (28-37 MBq) administration, normal rats and rats pretreated with haloperidol were imaged in a PET/CT scanner and subsequently studied ex vivo for (18)F-fallypride localization in the pancreas. A streptozotocin-treated diabetic rat model was used to study localization of (18)F-fallypride in the pancreas, in vitro and ex vivo. Rat islet cells were transplanted into the spleen and visualized using (18)F-fallypride PET. (18)F-fallypride bound to isolated islet cells and pancreatic sections with an endocrine or exocrine selectivity of approximately 4; selectivity was reduced by haloperidol, suggesting that binding was D(2)/D(3)R-specific. Chemical destruction of islets by streptozotocin decreased (18)F-fallypride binding in pancreas by greater than 50%, paralleling the decrease in insulin immunostaining. Uptake of (18)F-fallypride in the pancreas was confirmed by radiochromatography and was 0.05% injected dose/cm(3) as measured by PET/CT. The ratio of (18)F-fallypride uptake in the pancreas to reference tissue (erector spinae muscle) was 5.5. Rat islets transplanted into the spleen were visualized in vivo by (18)F-fallypride and confirmed by immunostaining. The ratio of spleen-transplanted islets to erector spinae muscle was greater than 5, compared with a ratio of 2.8 in untransplanted rats. These studies demonstrate the potential utility of (18)F-fallypride as a PET agent for islet cells.
    Journal of Nuclear Medicine 06/2011; 52(7):1125-32. · 5.77 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: MicroPET imaging studies using (18)F-nifene, a new positron emission tomography (PET) radiotracer for nicotinic acetylcholinergic receptors (nAChR) α4β2 receptors in rats, have been carried out. Rats were imaged for 90 min after intravenous injection of (18)F-nifene (0.8 to 1 mCi), and binding potential (BP(ND)) was measured. (18)F-Nifene binding to thalamic and extrathalamic brain regions was consistent with the α4β2 nAChR distribution in the rat brain. Using the cerebellum as a reference, the values for the thalamus varied less than 5% (BP(ND) = 1.30, n = 3), confirming reproducibility of (18)F-nifene binding. (18)F-Nifene microPET imaging was also used to evaluate effects of nicotine in a group of Sprague-Dawley rats under isoflurane anesthesia. Nicotine challenge postadministration of (18)F-nifene demonstrated reversibility of (18)F-nifene binding in vivo. For α4β2 nAChR receptor occupancy (nAChR(OCC)), various doses of nicotine (0, 0.02, 0.1, 0.25, and 0.50 mg/kg nicotine free base) 15 min prior to (18)F-nifene were administered. Low-dose nicotine (0.02 mg) reached > 80% nAChR(OCC) while at higher doses (0.25 mg) > 90% nAChR(OCC) was measured. The small amount of (18)F-nifene binding with reference to the cerebellum affects an accurate evaluation of nAChR(OCC). Efforts are underway to identify alternate reference regions for (18)F-nifene microPET studies in rodents.
    European journal of nuclear medicine and molecular imaging research. 06/2011; 1.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In this study, we compared two different D(2/3) receptor ligands, [¹⁸F]fallypride and [¹⁸F]desmethoxyfallypride ([¹⁸F]DMFP) with respect to the duration of the scan, visualization of extrastriatal receptors, and binding potentials (BP(ND) ) in the rat brain. In addition, we studied the feasibility of using these tracers following a period of awake tracer uptake, during which the animal may perform a behavioral task. Male Sprague-Dawley rats were imaged with [¹⁸F]fallypride and with [¹⁸F]DMFP in four different studies using microPET. All scans were performed under isoflurane anesthesia. The first (test) and second (retest) study were 150-min baseline scans. No retest scans were performed with [¹⁸F]DMFP. A third study was a 60-min awake uptake of radiotracer followed by a 90-min scan. A fourth study was a 150-min competition scan with haloperidol (0.2 mg/kg) administered via tail vein at 90-min post-[¹⁸F]fallypride injection and 60-min post-[¹⁸F]DMFP. For the test-retest studies, BP(ND) was measured using both Logan noninvasive (LNI) method and the interval ratios (ITR) method. Cerebellum was used as a reference region. For the third study, the binding was measured only with the ITR method, and the results were compared to the baseline results. Studies showed that the average transient equilibrium time in the dorsal striatum (DSTR) was at 90 min for [¹⁸F]fallypride and 30 min for [¹⁸F]DMFP. The average BP(ND) for [¹⁸F]fallypride was 14.4 in DSTR, 6.8 in ventral striatum (VSTR), 1.3 in substantia nigra/ventral tegmental area (SN/VTA), 1.4 in colliculi (COL), and 1.5 in central gray area. In the case of [¹⁸F]DMFP, the average BP(ND) values were 2.2 in DSTR, 2.7 in VSTR, and 0.8 in SN/VTA. The haloperidol blockade showed detectable decrease in binding of both tracers in striatal regions with a faster displacement of [¹⁸F]DMFP. No significant changes in BP(ND) of [¹⁸F]fallypride due to the initial awake state of the animal were found, whereas BP(ND) of [¹⁸F]DMFP was significantly higher in the awake state compared to baseline. We were able to demonstrate that dynamic PET using MicroPET Inveon allows quantification of both striatal and extrastriatal [¹⁸F]fallypride binding in rats in vivo. Quantification of the striatal regions could be achieved with [¹⁸F]DMFP.
    Synapse 01/2011; 65(8):778-87. · 2.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Brown adipose tissue [BAT] metabolism in vivo is vital for the development of novel strategies in combating obesity and diabetes. Currently, BAT is activated at low temperatures and measured using 2-deoxy-2-18F-fluoro-D-glucose [18F-FDG] positron-emission tomography [PET]. We report the use of β3-adrenergic receptor-mediated activation of BAT at ambient temperatures using (R, R)-5-[2-[2,3-(3-chlorphenyl)-2-hydroxyethyl-amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate, disodium salt [CL316,243] (a selective β3-adrenoceptor agonist) and measured by 18F-FDG PET/computed tomography [CT]. Control and CL316,243-treated (2 mg/kg) male Sprague-Dawley rats were administered with 18F-FDG for PET/CT studies and were compared to animals at cold temperatures. Receptor-blocking experiments were carried out using propranolol (5 mg/kg). Dose effects of CL316,243 were studied by injecting 0.1 to 1 mg/kg 30 min prior to 18F-FDG administration. Imaging results were confirmed by autoradiography, and histology was done to confirm BAT activation. CL316,243-activated interscapular BAT [IBAT], cervical, periaortic, and intercostal BATs were clearly visualized by PET. 18F-FDG uptake of IBAT was increased 12-fold by CL316,243 vs. 1.1-fold by cold exposure when compared to controls. 18F-FDG uptake of the CL-activated IBAT was reduced by 96.0% using intraperitoneal administration of propranolol. Average 18F-FDG uptake of IBAT increased 3.6-, 3.5-, and 7.6-fold by doses of 0.1, 0.5, and 1 mg/kg CL, respectively. Ex vivo 18F-FDG autoradiography and histology of transverse sections of IBAT confirmed intense uptake in the CL-activated group and activated IBAT visualized by PET. Our study indicated that BAT metabolic activity could be evaluated by 18F-FDG PET using CL316,243 at ambient temperature in the rodent model. This provides a feasible and reliable method to study BAT metabolism.
    EJNMMI research. 01/2011; 1(1):30.